ASSESSMENT OF BACULOVIRAL VS ADENOVIRAL VECTORS FOR GENE DELIVERY IN EXPERIMENTAL BRAIN CANCER

ASAD ANTONELA; PIEDRE MATIAS LUIS; SAGRIPANTI SOFIA; FALLIT MATIAS GARCIA; NICOLA CANDIA ALEJANDRO JAVIER; ZUCCATO CAMILA; IMSEN MERCEDES; ROMANOWSKI VICTOR; SEILICOVICH ADRIANA; ZANETTI FLAVIA; CANDOLFI MARIANELA

Mar del Plata

Congreso; 64 Meeting of the Argentine Society of Clinical Research; 2019

Gliomas are primary tumors of the central nervous system that arise from glial cells. They are classified according to their histopathologic characteristics from grade I to grade IV. Grade IV gliomas are very invasive and diffuse tumors, otherwise called glioblastomas (GB). GB are the most frequent and aggressive primary brain tumors in adults. Despite the advances in the neuro-oncology field, GB presents many therapeutic challenges and patients? prognosis remains dismal. Gene therapy consists of any procedure that modifies the patient?s genetics in order to treat or prevent a medical condition. Viral vectors are a good strategy for achieving stable and sustained expression and secretion of therapeutic molecules in the brain. Therapeutic transgenes can be locally expressed in the tumor bed after surgery where GB cells remain and give rise to recurrences. Recombinant adenoviral vectors (AdV) are non-replicative vectors capable of transducing dividing and quiescent cells. They can be produced in high titers and yield good transduction efficiency in the brain. Their main shortcoming is that they are very immunogenic and the general population exhibits pre-existing anti-AdV immunity, which leads to transient transgene expression. Baculoviral vectors (BV) are vectors that primarily infect insects at larval stage, but they can also transduce cells from other species. Even though BVs are less stable than AdVs after long-term storage, their advantage is that pre-existing immunity against BVs has not been reported in humans. Our hypothesis is that BVs may constitute a very useful tool for stable transgene expression in the brain. We constructed AdV and BV encoding the reporter gene tdtomato under the control of the CMV promoter. AdV and BV transduction efficiency was assessed by microscopy in vitro in GB cell lines, as well as in vivo after injection in the striatum of naïve or GB-bearing C57Bl/6 mice.